Identifying Mast Cells in Gastrointestinal Biopsies in Pediatric Irritable Bowel Patients

Abstract

Objectives: Mast cells (MCs) have been proposed to be involved in the pathophysiology of irritable bowel syndrome (IBS). Nonetheless, the quantity and distribution of MCs in the gastrointestinal tract of pediatric patients with IBS are not well defined. This study aimed to compare the number of MCs in children with and without IBS and to establish histopathological reference values in pediatrics. Methods: Forty-nine participants with IBS were prospectively enrolled and classified into IBS with atopy (n = 29) and IBS without atopy (n = 20). As our retrospective control group, we selected 42 individuals with a history of polyposis syndrome or gastroesophageal reflux disease with normal histopathology. Retrospective selection of the control cohort was performed in a manner similar to previously published adult and pediatric studies. MCs were prospectively stained immunohistochemically on specimens from the stomach, duodenum, terminal ileum, and descending colon of both groups. Results: The IBS group showed significantly more MCs per high-power field (MCs/HPF) in the stomach, duodenum, terminal ileum, and descending colon (P < 0.001), irrespective of their atopic status. Optimal MC cutoff values for IBS are ≥20.5 MCs/HPF in the stomach (area under the curve [AUC] = 0.84); ≥23.0 MCs/HPF in the duodenum (AUC = 0.79); ≥33.5 MCs/HPF in the terminal ileum (AUC = 0.82); and ≥22.5 MCs/HPF in the descending colon (AUC = 0.86). Conclusions: Pediatric patients with IBS showed increased numbers of MCs in the stomach, duodenum, terminal ileum, and descending colon when compared with controls. Further trials are needed to explain the role of MCs in pediatric IBS, which might facilitate the development of targeted therapeutic interventions.

Mast cell evaluation in gastrointestinal biopsies: should we be counting? A critical review and practical guide for the surgical pathologist

“…The findings in these and several other studies 27,[32][33][34][35][36] that report mean mast cell counts in excess of 20/hpf at various sites in the GI tract suggest that (1) the proposed upper limit of normal of 20/HPF for mast cells in GI biopsies is not applicable to biopsies stained with CD117, and (2) there is insufficient evidence to support mast cell counting in GI biopsies as part of the diagnostic work-up for chronic diarrhoea with no identified underlying cause.…”

“…42 Owing to their key role as inflammatory mediators and maintenance of normal gut function, mast cell numbers in GI biopsies have been extensively evaluated in IBS. Interestingly, a number of studies have reported an increased number of mucosal mast cells in patients with IBS relative to asymptomatic controls [34][35][36][37][38][39][40][41] ; indeed, in a large pooled meta-analysis of 22 studies, mast cells were found to be significantly increased in the descending (standardised mean difference [SMD]: 1.69 [95% confidence interval [CI]: 0.65-2.73]; P = 0.001) and rectosigmoid (SMD: 0.38 [95% CI: 0.06-0.71]; P = 0.02). 42 The large overlap in counts between patients with IBS and normal controls, however, limits the diagnostic utility of this observation, and other studies have found no significant differences in mast cell counts between patients with IBS and healthy controls.…”

What is new with irritable bowel syndrome

“…Mast cells have also been described in IBS. In a retrospective cohort study including 49 pediatric patients with IBS and 42 control patients, patients with IBS had a statistically significant increase of mast cells within the stomach, duodenum, terminal ileum, and descending colon, independent of systemic atopy [9 ▪ ].…”

“…IBS has been described as one type of FABD, along with functional dyspepsia, abdominal migraines and functional abdominal pain not otherwise specified (FAP-NOS), also termed disorders of gut-brain interactions (DGBIs) [3,4 ]. According to the Rome IV Pediatric Committee, IBS must include the following for at least 2 months prior to diagnosis: abdominal pain for at least 4 days out of a month associated with either defecation, a change in frequency of stools or appearance of stool; pain that is not relieved by defecation; and symptoms that cannot be explained by another condition after thorough evaluation.…”

“…Although not fully understood, IBS is thought to be because of multiple factors including abnormalities in gastrointestinal motility as well as visceral hypersensitivity, genetic predisposition, intestinal dysbacteriosis and increased intestinal permeability [4 ▪ –7 ▪ ,8,9 ▪ ].…”